Venoms are complex mixtures of biologically active components. The effect of a venom on a mammal is due to the interaction of these venom components with normal body processes. To understand how a venom causes problems, the venom must be fractionated and its toxic components identified, isolated, and characterized. Only after this knowledge is available can specific treatment of envenomation be accomplished. Also, purified venom components can be very useful. The four venoms which are being studied in this project are those obtained from the timber rattlesnake, Crotalus horridus horridus, the eastern cottonmouth. Agkistrodon piscivorus piscivorus, the northern copperhead, Agkistrodon contortrix mokasen, and the brown recluse spider, Loxosceles reclusa. All four of these venoms produce severe local tissue responses while the systemic effects of the snake venoms are comparatively mild. Three hemorrhage-inducing components have been identified in and purified from timber rattlesnake venom. These components will be further characterized and their mechanisms of action examined. The site of action of the lethal basic protein of this venom will be determined. Conditions to stabilize the systemic component of brown recluse spider venom will be described. Causes of the variability in northern copperhead will be determined. The most lethal fractions of eastern cottonmouth venom will be further separated and characterized.